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Verfasst von:Sun, Zhi-chuan [VerfasserIn]   i
 Han, Wen-Juan [VerfasserIn]   i
 Dou, Zhi-Wei [VerfasserIn]   i
 Lu, Na [VerfasserIn]   i
 Wang, Xu [VerfasserIn]   i
 Wang, Fu-Dong [VerfasserIn]   i
 Ma, Sui-Bin [VerfasserIn]   i
 Tian, Zhi-Cheng [VerfasserIn]   i
 Xian, Hang [VerfasserIn]   i
 Liu, Wan-Neng [VerfasserIn]   i
 Liu, Ying-Ying [VerfasserIn]   i
 Wu, Wen-Bin [VerfasserIn]   i
 Chu, Wen-Guang [VerfasserIn]   i
 Guo, Huan [VerfasserIn]   i
 Wang, Fei [VerfasserIn]   i
 Ding, Hui [VerfasserIn]   i
 Liu, Yuan-Ying [VerfasserIn]   i
 Tao, Hui-Ren [VerfasserIn]   i
 Freichel, Marc [VerfasserIn]   i
 Birnbaumer, Lutz [VerfasserIn]   i
 Li, Zhen-Zhen [VerfasserIn]   i
 Xie, Rou-Gang [VerfasserIn]   i
 Wu, Sheng-Xi [VerfasserIn]   i
 Luo, Ceng [VerfasserIn]   i
Titel:TRPC3/6 Channels Mediate Mechanical Pain Hypersensitivity via Enhancement of Nociceptor Excitability and of Spinal Synaptic Transmission
Verf.angabe:Zhi-Chuan Sun, Wen-Juan Han, Zhi-Wei Dou, Na Lu, Xu Wang, Fu-Dong Wang, Sui-Bin Ma, Zhi-Cheng Tian, Hang Xian, Wan-Neng Liu, Ying-Ying Liu, Wen-Bin Wu, Wen-Guang Chu, Huan Guo, Fei Wang, Hui Ding, Yuan-Ying Liu, Hui-Ren Tao, Marc Freichel, Lutz Birnbaumer, Zhen-Zhen Li, Rou-Gang Xie, Sheng-Xi Wu, and Ceng Luo
E-Jahr:2024
Jahr:[27 November 2024]
Umfang:22 S.
Illustrationen:Illustrationen
Fussnoten:Gesehen am 04.06.2025
Titel Quelle:Enthalten in: Advanced science
Ort Quelle:Weinheim : Wiley-VCH, 2014
Jahr Quelle:2024
Band/Heft Quelle:11(2024), 44, Artikel-ID 2404342, Seite 2404342-1-2404342-22
ISSN Quelle:2198-3844
Abstract:Patients with tissue inflammation or injury often experience aberrant mechanical pain hypersensitivity, one of leading symptoms in clinic. Despite this, the molecular mechanisms underlying mechanical distortion are poorly understood. Canonical transient receptor potential (TRPC) channels confer sensitivity to mechanical stimulation. TRPC3 and TRPC6 proteins, coassembling as heterotetrameric channels, are highly expressed in sensory neurons. However, how these channels mediate mechanical pain hypersensitivity has remained elusive. It is shown that in mice and human, TRPC3 and TRPC6 are upregulated in DRG and spinal dorsal horn under pathological states. Double knockout of TRPC3/6 blunts mechanical pain hypersensitivity, largely by decreasing nociceptor hyperexcitability and spinal synaptic potentiation via presynaptic mechanism. In corroboration with this, nociceptor-specific ablation of TRPC3/6 produces comparable pain relief. Mechanistic analysis reveals that upon peripheral inflammation, TRPC3/6 in primary sensory neurons get recruited via released bradykinin acting on B1/B2 receptors, facilitating BDNF secretion from spinal nociceptor terminals, which in turn potentiates synaptic transmission through TRPC3/6 and eventually results in mechanical pain hypersensitivity. Antagonizing TRPC3/6 in DRG relieves mechanical pain hypersensitivity in mice and nociceptor hyperexcitability in human. Thus, TRPC3/6 in nociceptors is crucially involved in pain plasticity and constitutes a promising therapeutic target against mechanical pain hypersensitivity with minor side effects.
DOI:doi:10.1002/advs.202404342
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

kostenfrei: Volltext: https://doi.org/10.1002/advs.202404342
 kostenfrei: Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/advs.202404342
 DOI: https://doi.org/10.1002/advs.202404342
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:mechanical pain hypersensitivity
 nociceptor
 synaptic potentiation
 TRPC3
 TRPC6
K10plus-PPN:192745283X
Verknüpfungen:→ Zeitschrift

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